The present invention is concerned with providing an advantageous method of treating an ovarian cancer by administering a pharmaceutically acceptable cadmium containing compound to a human or other mammalian patient suffering from an ovarian cancer.
Pharmaceutical compositions and Pharmaceutical kits which are useful in practicing the method of ovarian cancer treatment are also provided.
Cadmium is a highly toxic non-essential transition metal that constitutes an important potential health risk to the environment. Cadmium has been characterized as a potent carcinogen in animals, and is presumed to be carcinogenic in humans, as evidenced in epidemiological studies of workers occupationally exposed to this heavy metal [1]. Studies of the metabolism of Cadmium in rodent tissues and organs suggest that the mechanism of its toxic effect may be through induction of abnormal protein synthesis [3]. The modulation of Cadmium toxicity may be mediated through metallothionein and glutathione [4-7]. In cell culture, Cadmium has been shown to be cytotoxic [6, 8-10], mutagenic [10-13], and capable of inducing cellular transformation [3]. Cadmium interacts with cellular macromolecules and modifies the metabolism of DNA, RNA and protein [14], any of which could account for the cytotoxic effect of Cadmium at the molecular level. Surprisingly, several animal studies have shown that Cadmium is associated with suppression of tumor development. Waalkes and colleagues, examining the tumor promoting effect of Cd in B6C3F1 mice treated with the lung and liver tumor promotor N-nitrosodiethylamine (NDEA), unexpectedly found that Cadmium prevented NDEA-induced tumor formation [4,16]. In that study, it was shown that a single dose of NDEA followed by cadmium chloride in the drinking water, eliminated spontaneously-occurring liver tumors and reduced the incidence and multiplicity of NDEA-induced lung tumors in these mice. This Cadmium-induced tumor suppression effect on B6C3F1 mouse liver and lung occurred regardless of the time period of Cadmium administration.
These investigators suggested that the tumor suppressive effect of Cadmium may possibly be due to a specific toxicity toward previously xe2x80x9cinitiatedxe2x80x9d tumor cells within the mouse liver and lung. Histologic examination of NDEA-induced hepatic and pulmonary lesions in these mice revealed a marked and specific deficiency of metallothionein levels in tumor cells. In addition, the hepatic lesions responded abnormally to the induction of metallothionein compared to normal tissue surrounding the lesions. This suggests that transformation-initiated cells acquired this tumor suppression effect by Cadmium. The molecular mechanisms involved in the Cadmium-induced tumor suppression is unknown.
The present invention is concerned with providing an advantageous method for treating ovarian cancer in a human or other mammalian patient suffering from ovarian cancer, by administering to said patient an effective ovarian cancer treating amount of a pharmaceutically acceptable cadmium containing compound, optionally in combination with an effective ovarian cancer treating amount of cisplatin.
The present invention is also concerned with providing a pharmaceutical composition which comprises an effective ovarian cancer treating amount of a pharmaceutically acceptable cadmium containing compound, and a pharmaceutically acceptable carrier therefor, which may be used in practicing the advantageous method for treating ovarian cancer which is disclosed herein.
The present invention is also concerned with providing a kit which is useful in the treatment of ovarian cancer in a human or other mammalian patient suffering from ovarian cancer, wherein the kit comprises: (a) a pharmaceutical composition which comprises an effective ovarian cancer treating amount of a pharmaceutically acceptable cadmium containing compound, and a pharmaceutically acceptable carrier therefor, (b) optionally a pharmaceutical composition which comprises an effective ovarian cancer treating amount of cisplatin, and a pharmaceutically acceptable carrier therefor, and (c) instructions for providing an advantageous method for treating ovarian cancer in a human or other mammalian patient suffering from ovarian cancer, by administering to said patient the pharmaceutical composition comprising the effective ovarian cancer treating amount of the pharmaceutically acceptable cadmium containing compound, and optionally by administering in combination therewith to the patient the pharmaceutical composition comprising the effective ovarian cancer treating amount of cisplatin.